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Summary Electroclinical aspects of the West syndrome are studied in their atypical forms: clinical and EEG characteristics, partial forms, Aicardi syndrome. Etiological investigations (especially CT scan) are necessary to distinguish the more frequent ‘secondary forms’ from the ‘primary forms’: The etiological factors are: (i) Prenatal causes (hereditary affections, chromosome-related etiology, fetal etiology); (ii) Perinatal causes (prematurity, traumatic delivery); iii) Postnatal causes (infectious diseases). The evolutive aspects and prognosis are different for ‘primary’ and ‘secondary’ forms. The time of commencement of the mode of therapy and its duration are important factors in relation to the prognosis of ‘primary forms’. A pre-existing encephalopathy obviously leads to a very poor prognosis. A typical Lennox-Gastaut syndrome can be observed in infants. However, atypical forms are more frequent. These too have a poor prognosis because they are usually secondary to cerebral lesions.

The clinical picture of the Aicardi syndrome consists of a mentally retarded female infant with seizures, who lacks a corpus callosum and a pineal gland. There is Dandy-Walker malformation, vertebral anomalies, chorioretinopathy, coloboma, and heterotopia of gray matter. Since overdistention of the neural tube is the cause of each of these anatomic features, the same cause is responsible for the complete syndrome.

The Aicardi syndrome consists of agenesis of the corpus callosum, infantile spasms, a characteristic lacunar chorioretinopathy, mental subnormality, and costovertebral anomalies. All patients have been female. Its clinical similarity to several congenital intrauterine infections, particularly toxoplasmosis, is reinforced by the erroneous diagnosis of congenital infection initially made in the two patients reported here. Reasons for this confusion are outlined, and methods for a clinical differentiation between the Aicardi syndrome and the congenital infections are discussed.

The neuropathological examination of the brain of a 4-month-old girl with Aicardi syndrome (infantile spasms, chorioretinal lacunae, psychomotor retardation, agenesis of the corpus callosum and vertebral anomalies) showed agenesis of the corpus callosum, agenesis of the anterior commissure and abnormal orientation of the hippocampal formation, in addition to periventricular cerebral nodules and extensive non-laminated cortical polymicrogyria of the fronto-parietal regions and gyrus cinguli of both hemispheres. A non-communicating medial supracollicular cyst, racemose cysts of the choroid plexus, underdevelopment of the inferior cerebellar vermis tonsils were also observed. The study of the polymicrogyric cortex with the Golgi method revealed an abnormal orientation of neurons; but the different varieties of cells were located at the depth corresponding to that were they are normally found. The Golgy study of the periventricular nodules disclosed the presence of different types of cortex-like neurons. On the basis of these data it may be suggested that polymicrogyria is not a migratory disturbance, but rather the result of a partial necrosis of the cortical mantle occurring before the 5th month of foetal life.

Eighteen girls with Aicardi syndrome were identified through a survey of neurologists, geneticists, and ophthalmologists. All had infantile seizures, developmental delay, agenesis of the corpus callosum (complete: 72%, partial: 28%), and characteristic chorioretinal lacunar lesions. Costovertebral defects including hemivertebrae, scoliosis, and absent or malformed ribs were present in 39%, cortical heterotopias were present in 50%, and microphthalmia was identified in a third. Cytogenetic investigation was carried out in all families. An unbalanced X;3 translocation, 46,X,der(X)t(X;3)(p22.3;p23)mat, was discovered in a girl with chorioretinal lacunar lesions characteristic of Aicardi syndrome, developmental delay, and infantile seizures. However, this child had a normal appearing corpus callosum on CT and magnetic resonance imaging scans and therefore did not meet the criteria for inclusion in the study. Chromosomes of all other patients and parents were normal. Findings at birth, age of seizure onset, treatment, and prognosis are discussed. The pedigree data from these 18 families demonstrated an unaffected male:female sib ratio of 1:1.7 and a 14% spontaneous abortion rate. The findings of this study support the contention that Aicardi syndrome is an X-linked dominant disorder with early embryonic lethality in hemizygous males and that all cases represent new mutations.

During the last six years the author has seen three new cases of Aicardi's syndrome, which hitherto had only been diagnosed in a total of 15 to 20 cases. One child also had Handmann's anomaly (morning glory syndrome), another a disturbance of leucine metabolism. The ophthalmoscopic findings in the third child were pathogmonomic, so that it was possible to establish the diagnosis before the EEG showed the typical curves, and even before callosal agenesis was shown by CT or vertebral anomalies by X-ray examination.

Hopkins, I. J., Humphrey, I., Keith, C. G., Susman, M., Webb, G. C. and Turner, E. K. (1979). Aust. Paediatr. J., 278–280. the Aicardi syndrome in a 47, XXY male. The Aicardi syndrome is reported for the first time in a male child. His chromosomal analysis revealed a 47, XXY karyotype. This finding supports the suggestion that this condition is due to a newly mutated X-chromosomal dominant gene. The existence of a 47, XXY chromosomal constitution in this male allows heterozygous expressions of the gene as in the female.

A Japanese girl is reported who had the typical clinical features of Aicardi syndrome associated with embryonal carcinoma. She developed infantile spasms at approximately 4 weeks of age; her seizures were intractable in spite of treatment with numerous antiepileptic drugs and ACTH. At 22 months of age, her left cheek gradually became swollen. Laboratory findings were normal except for a marked increase of serum α-fetoprotein. A transoral biopsy of the tumor revealed an embryonal carcinoma. This patient is the first reported with Aicardi syndrome and embryonal carcinoma. The relationship between congenital malformations and neoplasms is discussed.

A case of Aicardi's syndrome is reported. A 12-year-old mentally handicapped female has all the characteristics of the syndrome: agenesis of the Corpus callosum; female infant with mental handicap, epilepsy, characteristic eye lesions, vertebral anomalies and abnormal EEG pattern. The results of supporting examination and investigations are noted.

Summary The psychomotor development achieved by two girls with the Aicardi syndrome is described. Until now this syndrome has been considered to produce a total dissociation from the environment in those affected. The results of early intervention, although not spectacular, are sufficient to recommend early stimulation in these children.

A 2-month-old infant with the typical clinical features of Aicardi syndrome (i.e., infantile spasms, chorioretinal lacunae, and agenesis of the corpus callosum) is reported. At 5 years of age, pathologic examination revealed cortical heterotopias, rostral agenesis of the corpus callosum, hypoplasia of the unilateral optic nerve, and bilateral cerebellar hemispheres. Cavum septum pellucidum was present. A literature review of 5 autopsied patients with this syndrome is included.

This 14-day-old Japanese girl demonstrated the classic features of Aicardi syndrome, including infantile spasms, agenesis of the corpus callosum, chorioretinopathy, microphthalmia, vertebral anomalies, electroencephalographic abnormalities, and severe mental retardation. Furthermore, she had a cleft lip and palate and a severe brain malformation due to semilobar-type holoprosencephaly. This patient is the second reported with Aicardi syndrome and associated cleft lip and posterior palate; she is the first patient with an additional severe brain malformation due to semilobar-type holoprosencephaly.

For Incontinentia pigmenti Bloch-Sulzberger (IP) and Aicardi syndrome, an X-linked dominant transmission with lethality in hemizygous males has been proposed. The typical transition from inflammation to verrucous hypertrophy and hyperpigmented skin areas in IP suggests a gradual replacement of defective cells by normal cells. This would imply a preferential inactivation of the X chromosome carrying the IP gene with a proliferative advantage of this cell population. We have confirmed this hypothesis by demonstrating that the same X chromosome is preferentially active in fibroblasts grown from normal and hyperpigmented skin of an affected girl. In contrast, X inactivation was random in a girl with Aicardi syndrome.

A patient with Aicardi's syndrome had the complete clinical picture of mental subnormality, convulsions, electroencephalographic disturbances, ocular anomalies, female sex, and agenesis of the corpus callosum. A second patient had the features of the syndrome, with microphthalmia and one patient had the features of the syndrome, with microphthalmia and one depigmented zone. In both cases and in Brihaye's case, no pineal gland was found. Since the epiphysis cerebri is important as a clock for sexual development, its absence may be incompatible with the development of a male fetus. The pathogenesis of the syndrome remains obscure. While an exogenous cause may be at work in some of the cases, the complex and stereotypical character of the symptoms plead for a hereditary origin.

A 2-month-old Japanese girl exhibited tonic seizure, agenesis of the corpus callosum, lacunar chorioretinopathy, vertebral anomalies, electroencephalographic abnormalities and a malignant tumor. Autopsy revealed a hepatoblastoma and severe brain malformations consisting of callosal agenesis, arhinencephaly, marked polymicrogyria and optic nerve anomalies. It was thought that the pathogenic factor in this case may exert its effect during the fourth or fifth week of intrauterine life, and then may continue until the beginning of neuronal migration (about 3 months). This is the first reported case of Aicardi syndrome associated with hepatoblastoma, and may provide a link between teratogenicity and oncogenicity.

X-linked dominant inheritance with lethality in hemizygous males is a rare mode of inheritance. The three best-known disorders which seem to be inherited in this way, are incontinentia pigmenti (IP) Bloch-Sulzberger, oral-facial-digital I (OFD I) syndrome, and focal dermal hypoplasia (FDH syndrome, Goltz syndrome). It is the purpose of this article to give a review of the clinical and genetic aspects of the above-mentioned diseases and to add those disorders in which this mode of inheritance is discussed. These disorders are: X-linked chondrodysplasia punctata (CP), cervico-oculo-acusticus syndrome (Wildervanck syndrome, COA), congenital cataract with microcornea or slight microphthalmia, muscular dystrophy--hemizygous lethal, partial lipodystrophy with lipatrophic diabetes and hyperlipidemia, Aicardi syndrome, coxo-auricular syndrome, and Johanson-Blizzard syndrome. OTC deficiency is included in the study, although there is no lethality in utero, only in the neonatal period. A critical evaluation of the current literature is carried out.

Aicardi's syndrome, which is characterized by agenesis of the corpus callosum, specific chorioretinal abnormalities, and defects of vertebrae and ribs, is considered a probable X-linked dominant trait with male lethality. All features of this syndrome were seen in a girl with a de novo balanced X/3 translocation (46,X,t(X;3)(p22;q12)). It is hypothesized that the clinical picture is the consequence of chromosome breakage within the Aicardi locus. Then, unusual X-inactivation patterns in blood and fibroblasts of this patient can be explained by somatic selection against cells with the Aicardi phenotype.

SUMMARY A case of Aicardi's syndrome is described. The main features are infantile spasms, pathognomonic chorioretinopathy, evidence of defects of the corpus callosum, cortical heterotopia, major dorsal vertebral anomalies, characteristic eeg changes, severe sub-normality, female sex and no family history. It is likely that this syndrome is not excessively rare. RESUME Le syndrome d'Aicardi Les auteurs rapportent un cas de syndrome d'Aicardi. Les principales caracteristiques sont: spasmes infantiles, chorioretinopathie pathognomonique; evidence d'une alttration du corps calleux; heterotopie corticale; anomalies majeures des vertebres dorsales; modifications caracteristiques a I'eeg; arrieration mentale; sexe feminin et pas de cass familiaux. II est vraisemblable que ce syndrome n'est pas excessivement rare. ZUSAMMENFASSUNG Das Aicardi Syndrom Es wird ein Fall mit Aicardi Syndrom beschrieben. Die wesentlichen Merkmale sind: fruhzeitig auftretende Spasmen; pathognomonische Chorioretinopathie; Zeichen von Corpus callosum-Defekten; Heterotopie der Corticalis; schwerwiegende Ruckenwirbel-anomalien; charakteristische eeg-Veranderungen; hochgradige Retardierung; weibliches Geschlecht und keine Familienanamnese. Wahrscheinlich ist dieses Syndrom gar nicht so extrem selten.

ccrcbrospinal fluid and other clinical specimens. J Clin Microblol 14:201, 1981. I I. Eisenach KD, French DE, Jimenez JF: Comparison of acridine orange and Gram stains for direct smears of cerebrospinal fluid. American Society for Microbiology Annual Meeting, Dallas, 1981. 12. Waring WW, .leansonne LO II1: Practical manual of pediatrics. St. Louis, 1982, CV Mosby, pp 454-5. 13. Sarff LD, Platt LH, McCracken GH: Ccrebrospinal fluid evaluation in neonates: Comparison of high-risk infants with and without meningitis. J PEDIATR 88:473, 1976. 14. Paik G: Reagents, stains, and miscellaneous test procedures. In Lennette Ell, editor: Manual of clinical microbiology. Washington, DC, 1980, American Society for Microbiology, p 1016.

In 1965 Aicardi et al . published a report on several children who had flexion spasms, agenesis of the corpus callosum and ocular anomalies. Since then many further reports have established the syndrome as a definite clinical entity, and other characteristic features are vertebral defects, mental retardation and hypsarrhythmia. Up till now all the reported cases have been females and it has been postulated that the condition is due to a mutation on the X chromosome which proves lethal in the hemizygous male. At the Royal Children’s Hospital, Melbourne a 2-mth-old male infant was admitted because of infantile spasms, and he was found to have ocular features strongly suggesting Aicardi Syndrome. These features are chorioretinal lacunae and colobomatous optic discs. The E.C.G. showed asynchronous activity between the 2 hemispheres and C.T. scanning indicated an absent corpus callosum. No evidence could be found of an intra-uterine infection and chromosomal studies showed a karyotype 47, XXY, indicating the Klinefelter Syndrome. This finding supports the hypothesis that the disease is due to an X-linked dominant trait.

The postmortem findings in a two month old infant with the typical clinical features of Aicardi syndrome (i.e., infantile spasms, chorioretinal lacunae, and agenesis of the corpus callosum) are reported from the Division of Neurology, Saitama Children’s Medical Center, Saitama, Japan.

To the Editor. —In the June 1989 issue of theArchives, Gloor et al 1 described a 19-month-old black female infant with a medical history of microcephaly, developmental delay, hypotonia, and seizures. The case was beautifully illustrated. Magnetic resonance imaging showed an arachnoidal cyst and partial agenesis of the corpus callosum. Funduscopic examination, according to the authors, revealed bilateral colobomatous discs. However, careful evaluation of the printed fundus photographs does not show optic disc colobomas but, rather, bilateral optic disc dysplasia and atypical peripapillary pigmentary changes. Moreover, the typical punched-out chorioretinal lesions were not present. These "punched-out" lesions are thought to be diagnostic of Aicardi's syndrome. 2 Also, the electroencephalogram (EEG) in the case did not show a pure hypsarrhythmia, highly characteristic of the Aicardi syndrome, 3,4 but a "pattern akin to it." Corpus callosum agenesis, arachnoidal cysts, and other neuroradiological midline anomalies have been described in patients with a